A biological fluid like human blood includes both cellular and noncellular components. The cellular components in blood include red blood cells (RBC), white blood cells (WBC), and platelets. Plasma is a non-cellular component of blood and is the liquid medium in which the cellular components are suspended.
It is well known that viruses, such as hepatitis or HIV virus, may be resident within human blood. The viruses residing in blood may be "intracellular," i.e. contained within one of the cellular components of blood, such as white blood calls, or they may be "extracellular," i.e. freely existing in the plasma. For example, the hepatitis virus is primarily an extracellular virus, the cytomegalovirus (the virus responsible for herpes) is primarily an intracellular virus, and the HIV virus (the virus responsible for AIDS) is found both intracellularly and extracellularly.
The medical community has developed methods and apparatus to remove virus from the blood stream or otherwise inactivate the virus.
A more recent approach to viral inactivation is the treatment of blood or blood components with a photochemical agent and light. When activated by light of an appropriate wavelength, the photochemical agent either kills the virus directly or indirectly inhibits the ability of the virus to replicate and, thus, in either case "inactivates" the virus. As used herein, the term "inactivate" (and ' forms thereof) mean the actual destructive, eradication of a contaminant such as a virus, or a direct or indirect effect on the contaminant that inhibits its ability to replicate or otherwise to adversely affect a living recipient.
Several known photochemical agents have been used or disclosed for use in inactivating viruses in blood. One such agent is methylene blue. As presently understood, a methylene blue molecule that has been activated by light becomes a catalyst for secondary and tertiary reactions that inactivate virus. More specifically, activation of the photochemical agent such as methylene blue is believed to result in the production of singlet oxygen which enhances the secondary and tertiary reactions. A detailed discussion of methylene blue, its photophysics, and photodynamic action on proteins, nucleic acid, viruses and bacteria is set forth in Tuit et al., "Photochemical interactions of methylene blue and analogues with DNA and other biological substrates," J. Photochea, Photobiol.B. Biol., 21, (1993) which is incorporated by reference herein.
In the development of light sources to illuminate methylene blue solutions so as to achieve a virucidal affect, there are many variables which can influence the photochemical yield of methylene blue excitation. Major variables include the wavelength of the light, the distance of the light source to the methylene blue solution, the geometry of the container containing the methylene blue, and the intensity of the light. It has been found difficult to reduce these variables to a single quantitative number, which can be used for standardization of light sources for methylene blue photochemistry and quality control/validation purposes.
For this and other reasons, the promise of photodynamic therapy in treating the nation's banked blood supply has gone largely unfulfilled.